pncA Resolved · high auto-curated
H37Rv Rv2043c · MTBC0 mtbc0_002176 ·
186 aa · 2317294–2317854 (-) ·
RefSeq NP_216559.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | pyrazinamidase/nicotinamidase PncA |
|---|---|
| MTBC0 PGAP re-annotation | pyrazinamidase PncA |
| Revised (this work) | Pyrazinamidase PncA. Pfam: Isochorismatase (PF00857.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6XD65
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Nicotinamidase/pyrazinamidase |
| EC (curated) |
EC 3.5.1.-, EC 3.5.1.19
|
| Curated function | Catalyzes the deamidation of nicotinamide (NAM) into nicotinate. Likely functions in the cyclical salvage pathway for production of NAD from nicotinamide (By similarity)..; FUNCTION: Is involved in the activation of the first-line antituberculous drug pyrazinamide (PZA) by converting it into the active form, pyrazinoic acid. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | pncA |
| eggNOG description | Isochorismatase family |
| Orthologous group | COG1335 |
| EC number |
EC 3.5.1.19
|
| KEGG orthology |
K08281
|
| KEGG pathways |
map00760, map01100
|
| Gene Ontology (39) |
GO:0003674, GO:0003824, GO:0005488, GO:0005506, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0006766, GO:0006767, GO:0006769, GO:0006807 +27 more
|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 5.304 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 31 missense, 1 nonsense, 2 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 0.39% of strains (571) · clonal |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Isochorismatase | PF00857.27 | 1.1e-29 | 3–182 | Isochorismatase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pncB1 (nicotinic acid phosphoribosyltransferase PncB1), high confidence from genomic context alone (score 988 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1330c pncB1 |
nicotinic acid phosphoribosyltransferase PncB1 | 994 | 988 ctx | fusion:567 cooccurence:654 database:900 textmining:585 |
Rv0573c pncB2 |
nicotinic acid phosphoribosyltransferase PncB2 | 987 | 977 ctx | fusion:410 cooccurence:572 database:900 textmining:475 |
Rv1151c cobB |
NAD-dependent protein deacylase | 927 | 917 | database:900 |
Rv3393 iunH |
nucleoside hydrolase | 928 | 913 | database:900 |
Rv3307 deoD |
purine nucleoside phosphorylase | 908 | 903 | database:900 |
Rv2042c hyp |
hypothetical protein | 943 | 888 ctx | neighborhood:882 textmining:514 |
Rv2041c |
sugar ABC transporter substrate-binding lipoprotein | 693 | 694 ctx | neighborhood:684 |
Rv2044c hyp |
hypothetical protein | 888 | 691 ctx | neighborhood:690 textmining:652 |
Rv2037c |
transmembrane protein | 674 | 675 ctx | neighborhood:664 |
Rv2040c |
sugar ABC transporter permease | 670 | 671 ctx | neighborhood:666 |
Rv2039c |
sugar ABC transporter permease | 669 | 670 ctx | neighborhood:666 |
Rv2038c ugpC |
sugar ABC transporter ATP-binding protein | 668 | 669 ctx | neighborhood:666 |
Rv3433c nnr |
bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase | 653 | 654 | coexpression:644 |
Rv2045c lipT |
carboxylesterase LipT | 576 | 575 ctx | neighborhood:569 |
Rv2982c gpdA2 |
glycerol-3-phosphate dehydrogenase | 522 | 505 | coexpression:412 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: pyrazinamidase/nicotinamidase PncA
- MTBC0 PGAP product: pyrazinamidase PncA
- Pfam (hmmscan --cut_ga): Isochorismatase PF00857.27 (E=1e-29)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_216559.1)
- Domains: Pfam-A via hmmscan --cut_ga — Isochorismatase (PF00857.27)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG1335 - Curated reference: UniProt I6XD65 (SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
101 functional partner(s); context anchor
pncB1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002176|Rv2043c|pncA MRALIIVDVQNDFCEGGSLAVTGGAALARAISDYLAEAADYHHVVATKDFHIDPGDHFSGTPDYSSSWPPHCVSGTPGADFHPSLDTSAIEAVFYKGAYTGAYSGFEGVDENGTPLLNWLRQRGVDEVDVVGIATDHCVRQTAEDAVRNGLATRVLVDLTAGVSADTTVAALEEMRTASVELVCSS